The role of Ca ions and cyclic AMP metabolism and structural alterations in the vascular smooth muscle in the pathogenesis of hypertension will be evaluated. Vascular tissue from spontaneously hypertensive rats (SHR) and Kyoto Wistar normotensive rats (NWR) between 3 and 12 weeks of age will be subjected to determinations of Ca ions binding by subcellular fractions, intracellular cyclic AMP levels, and morphological changes (hypertrophy of media) to determine if any of these changes precede hyperreactivity of vascular tissue to epinephrine in SHR. Enzymes of the cyclic AMP metabolic pathway influence Ca ions distribution and its effect on cell function. As such experiments have been designed to test the differences between vascular muscle of 12-14 weeks old SHR and NWR in: (a) the activity of cyclic AMP-dependent protein kinase and the ability of phosphorylated microsomes to bind Ca ions; (b) the binding characteristics of catecholamines to B-adrenergic receptors in cultured vascular smooth muscle cells from SHR and NWR and adenylate cyclase activity; (c) the activity of cyclic AMP phosphodiesterase and the regulatory mechanisms for its activation. As an extension of this study, the molecular changes observed in SHR will be compared with those present in another model of hypertension, the DOCA hypertensive rats.